NEW YORK, May 16 (Reuters) - Traumatic brain injury, the
signature wound of the Iraq and Afghanistan wars, is doubly
cruel: it leaves many victims emotionally shattered and
cognitively crippled. But because mild and moderate brain
injuries do not show up on CT or other imaging, doctors and even
family members are often skeptical that any real damage exists.

Now the first experiment of its kind documents exactly what
"the invisible injury" - at least the kind caused by blast waves
or repeated physical impacts - does to the brain: Crumpled
axons, which carry signals between neurons; gummed-up neurons
like those in Alzheimer's disease; strangled blood vessels.

An injured brain is so littered with the chewed-up remains
of neurons and other cells that "it looks like autophagy - the
brain eating itself alive," said Lee Goldstein, an Alzheimer's
researcher at the Boston University School of Medicine and
co-leader of the study.

The discovery promises to help such injuries be taken more
seriously, and might lead to preventives or treatments. It comes
at a time when both the Pentagon and the National Football
League are struggling with the legacy of head injuries.

Tens of thousands of U.S. troops have sustained such
injuries and some have committed suicide or other acts of
violence. In one horrific case, an Army staff sergeant who had
sustained head trauma is accused of murdering 17 Afghan
civilians in March.

The invisibility of many head injuries "is a huge problem,"
said retired U.S. Army General Peter Chiarelli, chief executive
officer of One Mind, a non-profit group promoting brain
research. "The ER doc will say, 'why am I wasting my time with
this guy when I have people with visible injuries?'"

Adding to the urgency: the recent suicides of former pro
football players who sustained head injuries during their
playing days. The most recent, former San Diego Chargers
linebacker Junior Seau, fatally shot himself earlier this month.

MAKING 'THE INVISIBLE INJURY' VISIBLE

For the new study, published Wednesday in the journal
Science Translational Medicine, scientists compared three groups
of brains. Four came from military veterans who had suffered the
blast of an improvised explosive device (IED) or a concussion.
Four belonged to young athletes who had concussions. And scores
were from mice that had been exposed to a blast akin to that
from an IED 17 feet (five metres) away packed with 12 pounds
(5.4 kilograms) of TNT, comparable to an IED made from a 120-mm
artillery round.

None of the brains had obvious injury. "If you hold them in
your hand you don't see any damage," said neuropathologist Ann
McKee of the Boston University School of Medicine and the
Veterans Affairs New England Healthcare System, co-leader of the
new study. "CT and MRI don't see it. It takes a microscope, even
an electron microscope."

With that scrutiny the damage was clear. Specialized cells
called astrocytes extended what BU's Goldstein called "little
feet" that wrapped themselves around blood vessels. Axons
crumbled and wound up in cellular garbage cans. Long strings of
proteins called tau formed, as seen in Alzheimer's disease.

The damage was strikingly similar to what scientists have
seen in the brains of ex-football players who had sustained head
injuries and, after death, were found to have chronic traumatic
encephalopathy (CTE), the condition once known as boxer's
dementia.

CTE can cause depression, aggression, impulsivity and memory
loss and has been linked to suicide. "Men become very
aggressive, develop a hair-trigger temper, and their judgment is
off," said Goldstein. "These are all part and parcel of damage
to the brain."

Age offered no protection. In the new study, the athletes
ranged in age from 17 to 27 when they died. They are the
youngest head-injury victims ever found with CTE.

Until this study, scientists could not be sure that head
injuries, from an IED or a linebacker, caused the brain or
behavioral changes. That's where the lab mice came in. While
anesthetized and in a special tube, they were exposed to blasts
akin to those suffered by U.S. troops in Iraq and Afghanistan.

Even though a shock wave barreled through the animals'
skulls at 336 miles per hour (541 kph), "there was no bleeding,
no contusions, no rips in the tissue," said Goldstein, who led
the mouse part of the study. "They looked for all the world like
what we see in human cases of traumatic brain injury - the
invisible injury that people have been talking about since World
War One."

The mice's behavior changed, too: they could not remember or
learn as well after the blast as before it. "This matches what
veterans (exposed to IEDs) say: 'I'm thinking slow and I can't
remember,'" said Goldstein.

The three lines of evidence - from veterans, athletes and
lab mice - suggest a common mechanism by which head injury
causes CTE and CTE impairs mental function.

Blasts in a war zone and head trauma on a gridiron both
break axons and stretch neurons, said McKee, a football fan who
has four bobble-head dolls of retired NFL quarterback Brett
Favre in her office. That stretching makes their membranes more
porous, allowing calcium ions to flood into the neuron and
activating enzymes that alter tau proteins just as they are
altered in Alzheimer's. As a result, said McKee, "the neuron is
no longer functional."

It may not even take such dramatic impacts to impair mental
skills. A second study released on Wednesday showed that some
college football and hockey players had lower scores on thinking
and memory tests after a season of enduring repeated but minor
hits to the head.

The players, outfitted with special helmets that measured
head impacts, experienced an average of 469 during the season,
scientists led by Thomas McAllister of the Geisel School of
Medicine at Dartmouth reported in the journal Neurology.

TREATING AND PREVENTING

There are no approved treatments for traumatic brain injury.
One experimental drug from BHR Pharma, a subsidiary of Besins
Healthcare SA, is in the last stage of human testing.

But the study suggests the military should re-examine
soldiers' protective gear. Heavy helmets that protect against
impacts and even bullets "are like putting a bowling ball on top
of a match stick," said Goldstein, exacerbating the destructive
acceleration and deceleration from a blast wave.

When the mice's heads were immobilized, though, an identical
blast produced no brain damage. That finding "has invaluable
implications for future safety measures," said psychologist
Jennifer Wilde of the University of Oxford, who was not involved
in the study. Namely: "special helmets to help keep soldiers
heads still during a blast."

The results also suggest that head trauma should be treated
immediately instead of waiting for symptoms. The BU scientists
"are working on field-deployable treatments," Goldstein said,
including anti-inflammatory drugs and agents that target leaky
blood vessels.

The U.S. military tries "to identify TBI as soon as possible
and provide effective treatment," said Pentagon spokesperson
Cynthia Smith. That policy pertains "regardless of whether the
injury is obvious and severe, or subtle and hidden." All service
members in a vehicle collision or rollover or within 150 feet
(46 metres) of a blast undergo a mandatory medical evaluation.

The new study also confirms the physical reality of
psychological illnesses that the military and others have
sometimes dismissed. "Post-traumatic stress disorder has been
regarded as a purely psychological illness, because we've been
looking at brains with CT and MRI," said neuropathologist Bennet
Omalu, chief medical examiner of San Joaquin County in
California and co-founder of the Brain Injury Research
Institute. BIRI hopes to examine Seau's brain, which the BU lab
is also in the running for.

"CT and MRI don't have the resolution to show the cellular
and sub-cellular changes you can get from a concussion or
sub-concussive injury," said Omalu. "Now we can see that PTSD is
likely to be a manifestation of traumatic brain damage."
(Reporting by Sharon Begley; Editing by Michele Gershberg and
Eric Beech)